Metabolic profiling reveals altered tryptophan metabolism in patients with kawasaki disease

Abstract

Kawasaki disease (KD) is a childhood vasculitis disease that is difficult to diagnose, and there is an urgent need for the identification of accurate and specific biomarkers. Here, we aimed to investigate metabolic alterations in patients with KD to determine novel diagnostic and prognostic biomarkers for KD. To this end, we performed untargeted metabolomics and found that several metabolic pathways were significantly enriched, including amino acid, lipid, and tryptophan metabolism, the latter of which we focused on particularly. Tryptophan-targeted metabolomics was conducted to explore the role of tryptophan metabolism in KD. The results showed that Trp and indole acetic acid (IAA) levels markedly decreased, and that l-kynurenine (Kyn) and kynurenic acid (Kyna) levels were considerably higher in patients with KD than in healthy controls. Changes in Trp, IAA, Kyn, and Kyna levels in a KD coronary arteritis mouse model were consistent with those in patients with KD. We further analyzed public single-cell RNA sequencing data of patients with KD and revealed that their peripheral blood mononuclear cells showed Aryl hydrocarbon receptor expression that was remarkably higher than that of healthy children. These results suggest that the Trp metabolic pathway is significantly altered in KD and that metabolic indicators may serve as novel diagnostic and therapeutic biomarkers for KD.

Alteration in kynurenine pathway metabolites in young women with autoimmune thyroiditis

“…Lim et al 18 showed that KP metabolites in the serum of patients with multiple sclerosis may have applications as disease biomarkers. The increased levels of KYN and KYNA have been postulated as novel diagnostic biomarkers for Kawasaki disease in children 51 . Park et al 24 suggested that serum KYN/TRP ratio can be a potential biomarker of fatigue in the primary Sjögren's syndrome.…”